rs2140148

Variant names:

• chr2-203707417-A-C
• rs2140148
• NM_006139.4:c.52+669A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-203707417-A-C
• chr2-203707417-A-G
• chr2-203707417-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006139.4(CD28):​c.52+669A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,214 control chromosomes in the GnomAD database, including 1,639 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1639 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392
• Publications: 11 publications found

Genes affected

CD28 (HGNC:1653): (CD28 molecule) The protein encoded by this gene is essential for T-cell proliferation and survival, cytokine production, and T-helper type-2 development. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

CD28 Gene-Disease associations (from GenCC):

• immunodeficiency 123 with HPV-related verrucosis

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD28	NM_006139.4	c.52+669A>C		intron_variant	Intron 1 of 3	ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.94+800A>C		intron_variant	Intron 1 of 3		NP_001397910.1
CD28	NM_001243077.2	c.52+669A>C		intron_variant	Intron 1 of 3		NP_001230006.1
CD28	NM_001243078.2	c.52+669A>C		intron_variant	Intron 1 of 2		NP_001230007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD28	ENST00000324106.9	c.52+669A>C		intron_variant	Intron 1 of 3	1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000458610.6	c.94+800A>C		intron_variant	Intron 1 of 3	1		ENSP00000393648.2
CD28	ENST00000374481.8	c.52+669A>C		intron_variant	Intron 1 of 2	1		ENSP00000363605.4
CD28	ENST00000718458.1	c.94+800A>C		intron_variant	Intron 1 of 2			ENSP00000520836.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20042 AN: 152092 Hom.: 1639 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.132 AC: 20052 AN: 152214 Hom.: 1639 Cov.: 32 AF XY: 0.130 AC XY: 9692 AN XY: 74396

African (AFR) AF: 0.0364 AC: 1511 AN: 41560

American (AMR) AF: 0.166 AC: 2536 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 921 AN: 3460

East Asian (EAS) AF: 0.115 AC: 596 AN: 5186

South Asian (SAS) AF: 0.0561 AC: 271 AN: 4828

European-Finnish (FIN) AF: 0.138 AC: 1465 AN: 10578

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12091 AN: 67994

Other (OTH) AF: 0.162 AC: 342 AN: 2112

Alfa AF: 0.160 Hom.: 2766

Bravo AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.23
DANN	Benign	0.69
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2140148; hg19: chr2-204572140;